Tag Archive for Beveridge

Researchers’ Paper Selected as “Editor’s Choice” by American Chemical Society

jp-2016-11976k_0007Three faculty and one graduate student co-authored a paper titled “Statistical Coupling Analysis combined with all-atom Molecular Simulation Postulates Dynamical Allosterism in the MutS DNA Mismatch Repair Protein,” published in the March issue of the Journal of Physical Chemistry – Biophysics, published by The American Chemical Society.

The authors include David Beveridge, the Joshua Boger University Professor of the Sciences and Mathematics, professor of chemistry, professor of integrative sciences; Manju Hingorani, professor of molecular biology and biochemistry, professor of integrative sciences; Kelly Thayer, visiting assistant professor of computer science; and molecular biology and biochemistry graduate student Bharat Lakhani.

This project is part of Lakhani’s ’16 PhD thesis of Lakhani. Notably, the project brings together the experimental biochemistry of Hingorani’s research program, which specializes in DNA mismatch repair, and the computational biophysics in Beveridge’s Laboratory, which specializes in molecular dynamics simulations. All theoretical calculations were carried out using the Wesleyan High Performance Computer Cluster.

In addition, the article was selected as an ACS “Editor’s Choice,” an honor given to one article from the entire ACS portfolio of journals each day of the year. As a consequence, the authors have been invited to submit a 30-40 minute online presentation to “ACS LiveSlides,” which increases the exposure of the published work.

Hingorani Awarded Major NIH Research Grant

Manju Hingorani, professor of molecular biology and biochemistry, was awarded a grant of $408,609 from the National Institutes of Health (NIH) to study the structure and mechanisms of DNA repair proteins responsible for fixing errors in the genetic code and preventing carcinogenesis.

The three-year grant will fund PhD and undergraduate students’ research on DNA mismatch repair (MMR). MMR corrects base mismatches and loops in DNA, and is therefore a critical guardian of genetic and cellular integrity. Defects in this essential, evolutionarily conserved DNA repair process cause high levels of mutations in the genome, which in turn lead to cancer. In humans, MMR defects manifest most frequently in a hereditary disorder known as Lynch Syndrome (LS), which substantially raises the risk of colorectal, endometrial and many other cancers.

A large number of MMR defects occur due to small, single-amino-acid changes in the MutS protein that initiates the repair reaction. Hinagorani’s research group has been investigating MMR proteins for the past 15 years. The group now has a detailed enough understanding of the MutS biochemical mechanism to determine how changing single amino acids affects MutS structure and function enough to disrupt MMR. In addition to experimental research, the project also builds on computational modeling done in collaboration with Joshua Boger University Professor of the Sciences and Mathematics David Beveridge’s group in the Chemistry Department, and Professor Saraswathi Vishveshwara’s group at the the Indian Institute of Science in Bangalore, India. Beverage is also professor of chemistry. The researchers hope that by applying biochemical, biophysical and computational approaches in an interdisciplinary manner, students will gain new knowledge about MutS function and, thereby, a better understanding of the basis for its malfunction in cancer.

Beveridge Elected to Academy of Science and Engineering

David Beveridge

David Beveridge

University Professor of Natural Science and Mathematics David Beveridge was one of 33 leading experts in science, engineering and technology recently elected to membership in the Connecticut Academy of Science and Engineering. The new members will be introduced at the Academy’s 38th annual meeting and dinner on May 22 at Quinnipiac University in Hamden, Conn.

According to the Academy, election is “on the basis of scientific and engineering distinction achieved through significant contributions in theory or applications, as demonstrated by original published books and papers, patents, the pioneering of new and developing fields and innovative products, outstanding leadership of nationally recognized technical teams, and external professional awards in recognition of scientific and engineering excellence.”

Beveridge is in the Chemistry Department and Molecular Biophysics Program. He has taught at Wesleyan since 1986, and served as Dean of Natural Sciences and Mathematics from 1992-1999. He has authored or co-authored more than 200 scientific papers. His research interests include theoretical physical chemistry and molecular biophysics, structural biology and bioinformatics, quantum mechanics, statistical thermodynamics, molecular dynamics and Monte Carlo computer simulation, and the role of water in structural biochemistry.

Hingorani Group Publishes 8 Papers on DNA Mismatch Repair

A research group led by Manju Hingorani, associate professor of molecular biology and biochemistry, has published eight papers in 2011-2012 on the mechanisms of DNA replication and repair proteins, independently and in collaboration with research groups at Wesleyan and other national and international universities.

The papers are:

“Large conformational changes in MutS during DNA scanning, mismatch recognition and repair signaling,” published in The EMBO Journal, 2012 (in press).

The Variable Sub-domain of Escherichia coli SecA functions to regulate in the SecA ATPase Activity and ADP release,” published in the Journal of Bacteriology, 2012 (March 2 Epub). Don Oliver, the Daniel Ayres Professor of Biology, professor of molecular biology and biochemistry, was the lead investigator and Fred Cohan, professor of biology, professor of environmental studies, was a co-author on this paper.

Single-molecule multiparameter fluorescence spectroscopy reveals directional MutS binding to mismatched bases in DNA,” published in Nucleic Acids Research, 2012 (Feb, 24 Epub).

Biochemical analysis of the human mismatch repair proteins hMutSαMSH2G674A-MSH6 and MSH2-MSH6T1219D,” published in the Journal of Biological Chemistry, 2012 (Jan. 25 Epub).

ATP Binding and Hydrolysis-Driven Rate-Determining Events in the RFC-Catalyzed PCNA Clamp Loading Reaction,” published in the Journal of Molecular Biology, Feb. 17, 2012; 416(2), pages 176-91.

A Central Swivel Point in the RFC Clamp Loader Controls PCNA Opening and Loading on DNA,” published in the Journal of Molecular Biology, Feb. 17, 2012; 416(2), pages 163-75.

Human MSH2 (hMSH2) protein controls ATP processing by hMSH2-hMSH6,” published in the Journal of Biological Chemistry, Nov. 18, 2011; 286(46), pages 40287-95.

Dynamical allosterism in the mechanism of action of DNA mismatch repair protein MutS,” published in the Biophysical Journal, Oct. 5, 2011;101(7), pages 1730-9. David Beveridge, the Joshua Boger Professor of the Sciences and Mathematics, was the lead investigator on this paper.

DNA Studies by Hingorani, Beveridge Published in Journals

Manju Hingorani, associate professor of molecular biology and biochemistry, co-authored a study titled “hMSH2 controls ATP processing by hMSH2-hMSH6,” published in the Journal of Biological Chemistry on Sept. 19. The abstract is online here.

Hingorani co-authored another study with David Beveridge, the Joshua Boger University Professor of the Sciences and Mathematics, professor of chemistry, titled “Allosterism in Muts Proteins: How DNA Mismatch Recognition Signals Repair.” The study was published in the Biophysical Journal in 2011. The abstract is online here.

Beveridge Guest Lectures at Institute in New Delhi

Becky Lee '10 and Professor David Beveridge at the Institute of Technology in New Delhi, India.

David Beveridge, the Joshua Boger University Professor of Natural Sciences and Mathematics, professor of chemistry, was on sabbatical last spring at the Indian Institute of Technology (IIT) in New Delhi, India. He was visiting and working on research projects with Professor B. Jayaram, director of the Supercomputer Center for Bioinformatics, SCFBIO.

Beveridge’s former student, Becky Lee ’10, was spending a year doing research in Jayaram’s SCFBIO research group on a project in computational biophysics.

Beveridge presented one of the thematic lectures on “Dynamic Allosterism” in a lecture series celebrating the 50th anniversary of IIT-Delhi.

NIH Supports Molecular Biophysics, Biological Chemistry Program

David Beveridge, the Joshua Boger University Professor of the Sciences and Mathematics, professor of chemistry, received a five year graduate student training grant from the National Institutes of Heath (NIH) in support of Wesleyan’s interdepartmental program in Molecular Biophysics and Biological Chemistry (MBBC). This program is co-coordinated by Ishita Mukerji, professor of molecular biology and biochemistry, director of graduate studies.

The MBBC Program involves 12 faculty members from chemistry, biology, MB&B and physics departments along with both graduate Ph.D. students and undergraduate certificate students. The grant, worth $662,820, is the latest in a series of awards to this program, which has been supported by the NIH since 1988.

Beveridge Honored at Biophysics Retreat

David Beveridge, the Joshua Boger University Professor of the Sciences and Mathematics., professor of chemistry, was honored at Wesleyan University’s 11th Annual Molecular Biophysics and Biological Chemistry Retreat Sept. 23. Beveridge came to Wesleyan about 30 years ago to develop a program in molecular biophysics within the Department of Chemistry. He studies how the structure, dynamic and solvation of nucleic acids and proteins influence binding and recognition. Pictured is Wesleyan President Michael Roth with Beveridge at the retreat.

NSF Grant Improves Numerical Modeling Capacity at Wesleyan

Francis Starr, associate professor of physics, co-authored a grant proposal, which was recently funded by the NSF to support growth of the computer facilities for the university’s Scientific Computing and Informatics Center.

A $298,736 grant from the National Science Foundation (NSF) will allow Wesleyan to remain competitive in numerical modeling research and education on an international level.

Francis Starr, associate professor of physics, David Beveridge, the Joshua Boger University Professor of the Sciences and Mathematics, and Michael Weir, professor of biology, director of the Hughes Program in the Life Sciences, received the grant for a project titled “Major Research Instrumentation – Recovery and Reinvestment program (MRI-R2): Acquisition of Shared Cluster and Database Computing Facilities at Wesleyan University.”

The grant, awarded over three years beginning May 1, will fund growth of the computer facilities for the university’s Scientific Computing and Informatics Center (SCIC), including expansion of the university’s high-performance computer cluster and a new genomics database server.

Wesleyan currently runs 36 Dell computer nodes for the academic computing cluster known as “Swallowtail.” Each machine is capable of processing eight jobs simultaneously, for a total of 288 jobs. Another 129 computer nodes called “Sharptail,” recently donated by Blue Sky Studios, are capable of processing two jobs simultaneously each, for a total of 258 jobs.

“With the NSF grant, we anticipate roughly doubling our capacity,” Starr says. “Think of it as setting up a virtual laboratory in the computer where we can perform experiments that might be challenging

NSF Grant Funds Cluster, Database Facilities

Francis Starr, associate professor of physics; David Beveridge, the Joshua Boger University Professor of the Sciences and Mathematics; and Michael Weir, professor of biology, director of the Hughes Program in the Life Sciences, received a grant from the National Science Foundation for a project titled “MRI-R2: Acquisition of Shared Cluster and Database Computing Facilities at Wesleyan University.” The grant, worth $298,736, will be awarded over three years beginning May 1, 2010. The grant was awarded as part of the American Recovery and Reinvestment Act of 2009.

NSF Awards Grant to Dierker, Beveridge

Lisa Dierker, chair and professor of psychology, and David Beveridge, the University Professor of the Sciences and Mathematics, professor of chemistry, received a $174,999 grant from the National Science Foundation. The grant will support an inquiry based, supportive approach to statistical reasoning and applications. The award will be applied Jan. 1, 2010 through Dec. 31, 2012.

NIH Renews Biophysics Training Support

David Beveridge, the University Professor of the Sciences and Mathematics, professor of chemistry, received a National Institutes of Health grant renewal to support the Molecular Biophysics Training Program. Wesleyan is the only liberal arts college to have such a program. The grant will support the program for an additional three years.